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Multiple MyelomaPhase 2NCT03221634

Efficacy and Safety Study of Pembrolizumab (MK-3475) in Combination With Daratumumab in Participants With Relapsed Refractory Multiple Myeloma (MK-3475-668/KEYNOTE-668)

A Phase 2 study testing Pembrolizumab and Daratumumab in people with Multiple Myeloma, run by Merck Sharp & Dohme LLC at 23 sites in 6 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with daratumumab in participants with relapsed refractory multiple myeloma (rrMM). The primary outcome measure for this study is the assessment of Objective Response Rate (ORR) in participants with rrMM. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Pembrolizumab and Daratumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
23 sitesin 6 countries
Study dates
1 Aug 2017to 10 Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a confirmed diagnosis of active MM and measurable disease defined as: a.) Serum M-protein levels ≥0.5 g/dL or b.) Urine M-protein levels ≥200 mg/24 hours or c.) For participants without measurable serum and urine M-protein levels, an abnormal serum free light chain ratio (FLC κ/λ) with involved FLC level ≥100 mg/L.
  • Has undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and must have failed their last line of treatment defined as lack of response or documented disease progression during or within 60 days of completing their last anti-myeloma therapy.
  • Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD; i.e., lenalidomide, thalidomide, or pomalidomide) AND a proteasome inhibitor (PI; i.e., bortezomib, ixazomib, or carfilzomib) alone or in combination and participant must have failed therapy with an IMiD or PI or both.
  • Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Has adequate organ function.
  • Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants must not be pregnant, breastfeeding, and must agree to use (or have their partner use) acceptable contraception during heterosexual activity during the treatment period and for at least 120 days after the last dose of study treatment.

Who cannot join

  • Has oligo-secretory myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström's macroglobulinemia, or any history of plasma cell leukemia.
  • Has a history of repeated infections, primary amyloidosis, hyperviscosity, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
  • Has known meningeal involvement of MM.
  • Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or daratumumab and any of its excipients.
  • Has known allergies, hypersensitivity, or intolerance to monoclonal antibodies (mAbs) or human proteins, or their excipients, or known sensitivity to mammalian-derived products.
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  • Has an active autoimmune disease that has required systemic treatment in past 2 years.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has either of the following: a.) Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal, or b.) Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of hepatitis B or known active hepatitis C.
  • Has a known history of active tuberculosis (TB).
  • Has received prior solid organ transplant.
  • Has clinically significant cardiac disease or electrocardiogram (ECG) abnormalities or any history of clinically significant ventricular arrhythmias.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
  • Has previously received daratumumab or other anti-cluster of differentiation 38 (anti-CD38) therapies.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK-3475) clinical study.
  • Has received prior anti-myeloma therapy including but not limited to dexamethasone, IMiDs, PIs, monoclonal antibody, chemotherapy, or radiation therapy within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (≤ Grade 1 or at Baseline) from AEs due to previously administered agents.
  • Has undergone prior allogeneic stem cell transplant (allo-SCT) within the last 5 years.
  • Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first dose of study treatment or are planning for or are eligible for auto- or allo-SCT.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Trial locations and contacts

23 sites in 6 countries.

23 sites in 6 countries

Canada6 sites

  • Calgary Lab Services - Foothills Medical Centre ( Site 0105)

    Calgary, Alberta, H9H 4M7

  • Cross Cancer Institute ( Site 0104)

    Edmonton, Alberta, H9H 4M7

  • Capital Health Queen Elizabeth II Health Sciences Centre ( Site 0101)

    Halifax, Nova Scotia, H9H 4M7

  • Hopital Maisonneuve-Rosemont [Montreal, Canada] ( Site 0102)

    Montreal, Quebec, H9H 4M7

  • McGill University Health Centre ( Site 0100)

    Montreal, Quebec, H9H 4M7

  • CHU de Quebec - Hopital de l'Enfant-Jesus ( Site 0106)

    Québec, Quebec, H9H 4M7

Other trials in Canada

Spain5 sites

  • Hospital Universitari Germans Trias i Pujol ( Site 0302)

    Badalona

  • Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0303)

    L'Hospitalet de Llobregat

  • Clinica Universitaria de Navarra ( Site 0301)

    Pamplona

  • Hospital Clinico Universitario de Salamanca ( Site 0300)

    Salamanca

  • Hospital Clinico Universitario de Valencia ( Site 0304)

    Valencia

Other trials in Spain

Israel4 sites

  • Rambam Medical Center ( Site 0700)

    Haifa

  • Rabin Medical Center ( Site 0702)

    Petah Tikva

  • Sourasky Medical Center ( Site 0701)

    Tel Aviv

  • Sheba MC ( Site 0703)

    Tel HaShomer

Other trials in Israel

United States3 sites

  • Emory University School of Medicine ( Site 0002)

    Atlanta, Georgia, 30322

  • Karmanos Cancer Institute ( Site 0001)

    Bloomfield Hills, Michigan, 48302

  • Mayo Clinic Jacksonville ( Site 0003)

    Jacksonville, Florida, 32224

Other trials in United States

France3 sites

  • CHRU Lille Hospital Claude Huriez ( Site 0200)

    Lille

  • Hopital Saint-Louis ( Site 0202)

    Paris

  • Centre Hopitalier Lyon Sud ( Site 0201)

    Pierre-Bénite

Other trials in France

Sweden2 sites

  • Skaenes Universitetssjukhus Lund ( Site 0500)

    Lund

  • Karolinska Universitetssjukhuset ( Site 0501)

    Stockholm

Other trials in Sweden

About this study

Official title: A Phase 2 Study of Pembrolizumab in Combination With Daratumumab (Anti CD38) in Participants With Relapsed Refractory Multiple Myeloma (rrMM)

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with daratumumab in participants with relapsed refractory multiple myeloma (rrMM). The primary outcome measure for this study is the assessment of Objective Response Rate (ORR) in participants with rrMM.

Read the detailed description

Study treatment will continue until the participant has completed 35 infusions (approximately 2 years) of pembrolizumab treatment. All participants who stop study treatment with stable disease (SD) or better may be eligible for up to an additional ~1 year of study treatment if they progress after stopping study treatment from the initial treatment phase.

Keywords
Programmed cell death 1 receptor (PD1), PD-1, Programmed cell death ligand 1 receptor (PDL1), PD-L1
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03221634
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants receive pembrolizumab 200 mg by intravenous (IV) infusion once every 3 weeks (Q3W) for up to 35 administrations (up to approximately 2 years) and receive daratumumab 16 mg/kg by IV infusion on Days 1, 8, 15, and 22 of Cycles 1-2; on Days 1 and 15 of Cycles 3-6, and on Day 1 of Cycle 7 and beyond, for up to 2 years. Each cycle is 28 days long.
Receives: Biological: Pembrolizumab; Biological: Daratumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    ORR is defined as the percentage of participants who experience a partial response (PR; ≥50% reduction of serum myeloma (M)-protein plus reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours) or better per International Myeloma Working Group (IMWG) 2016, based on investigator assessment.

    Measured: Up to approximately 2 years

Secondary outcomes (4)

  1. Disease Control Rate (DCR)

    DCR is defined as the percentage of participants who experience stable disease (SD; not meeting criteria for complete response, very good partial response, partial response, minimal response or progressive disease) or better prior to any evidence of progression, per IMWG 2016 based on investigator assessment.

    Measured: Up to approximately 2 years

  2. Duration of Response (DOR)

    DOR is defined as the time from first documented evidence of at least a PR (≥50% reduction of serum M-protein plus reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours) until disease progression or death, per IMWG 2016, based on investigator assessment.

    Measured: Up to approximately 2 years

  3. Adverse Events (AEs)

    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing one or more AEs will be assessed.

    Measured: Up to approximately 27 months

  4. Study Treatment Discontinuations Due to AEs

    The number of participants discontinuing study treatment due to AEs will be assessed.

    Measured: Up to approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2017
  2. Study start1 Aug 2017 (estimated)
  3. Primary completion20 Mar 2019 (estimated)
  4. Study completion10 Jun 2021 (estimated)

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03221634
Sponsor's protocol ID
3475-668
Other IDs
2017-001001-32, 2017
Status last verified
Mar 2019
First submitted
17 Jul 2017
Last updated
25 Mar 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Daratumumab in people with Multiple Myeloma, run by Merck Sharp & Dohme LLC at 23 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Canada, Spain, Israel, United States, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Up to approximately 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03221634.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2019.

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